9-74948171-C-A

Position:

• chr9-74948171-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017998.3(C9orf40):​c.462G>T​(p.Gln154His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C9orf40 NM_017998.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989

Genes affected

C9orf40 (HGNC:23433): (chromosome 9 open reading frame 40)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C9orf40	NM_017998.3	c.462G>T	p.Gln154His	missense_variant	2/2	ENST00000376854.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C9orf40	ENST00000376854.6	c.462G>T	p.Gln154His	missense_variant	2/2	1	NM_017998.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0073	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.061	P
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.37		Gain of phosphorylation at Y150 (P = 0.2312);
MVP		0.45
MPC		1.8
ClinPred		0.93	D
GERP RS		6.0
Varity_R		0.34
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2769058; hg19: chr9-77563087;